Effects of Fish Oil Combined with Selenium and Zinc on Learning and Memory Impairment in Aging Mice and Amyloid Precursor Protein Processing.
Biol Trace Elem Res. 2020 Jul 14. Epub 2020 Jul 14. PMID: 32666432
Alzheimer's disease is characterized by the aggregation of amyloid-beta (Aβ) peptide into plaques and neurofibrillary tangles. Aβ peptide is generated by the cleavage of the β-amyloid precursor protein (APP) by β- and γ-secretase. The present study was conducted to investigate the effects of fish oil (or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), selenium, and zinc on learning and memory impairment in an aging mouse model and on APP. We performed the Morris water maze and platform recorder tests on male Kunming mice (10/group) grouped as control and D-galactose-induced aging model mice treated with vehicle, fish oil, fish oil + selenium, fishoil + selenium + zinc, and positive control (red ginseng extract). Fish oil + zinc + selenium for 7 weeks significantly improved learning and memory impairments in aging model animals in the Morris water maze and platform recorder tests, as evidenced by shortened incubation periods and number of errors. In vitro analysis of Aβcontent in APP695-transfected CHO cells revealed a decrease after treatment with EPA, DHA, and their combinations with selenium or selenium and zinc. Assayingβ- and γ-secretase activities revealed a decrease in PCcells and mouse serum as well as a decrease inβ-site APP-cleaving enzyme 1 and presenilin 1 protein levels in the PCcells and mouse serum. Taken together, our results show that fish oil combined with selenium and zinc inhibited APP processing and alleviated learning and memory impairment in a mouse model of aging.